Peroxiredoxins (Prxs) are a ubiquitous class of thiol-dependent peroxidases that play an important role in the protection and response of cells to oxidative stress. The catalytic unit of typical 2-Cys Prxs are homodimers, which can self-associate to form complex assemblies that are hypothesized to have signaling and chaperone activity. Mitochondrial Prx3 forms dodecameric toroids, which can further stack to form filaments, the so-called high-molecular-weight (HMW) form that has putative holdase activity. We used single-particle analysis and helical processing of electron cryomicroscopy images of human Prx3 filaments induced by low pH to generate a ∼7-Å resolution 3D structure of the HMW form, the first such structure for a 2-Cys Prx. The pseudo-atomic model reveals interactions that promote the stacking of the toroids and shows that unlike previously reported data, the structure can accommodate a partially folded C terminus. The HMW filament lumen displays hydrophobic patches, which we hypothesize bestow holdase activity.
Radjainia, Mazdak, Hariprasad Venugopal, Ambroise Desfosses, Amy J. Phillips, N. Amy Yewdall, Mark B. Hampton, Juliet A. Gerrard, and Alok K. Mitra. "Cryo-electron microscopy structure of human peroxiredoxin-3 filament reveals the assembly of a putative chaperone." Structure 23, no. 5 (2015): 912-920.
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